By transferring hematopoietic stem cells (aged HSCs) to the environment of young mice (bone marrow niche), it has been shown that the stem cell gene expression pattern is rejuvenated relative to young hematopoietic stem cells. On the other hand, the function of older HSCs has not recovered in the niche of young bone marrow. The epigenome (DNA methylation) of aged HSCs did not change significantly even in the niche of young bone marrow, and DNA methylation profiles were found to be a better index than the gene expression pattern of older HSCs.
A research group led by Professor Atsushi Iwama of the Department of Stem Cells and Molecular Medicine, Institute of Medical Sciences, University of Tokyo (IMSUT) published these first world results and published in Journal of Experimental Medicine (online) November 24th.
The results will contribute to the development of treatments for age-related blood diseases. “
Professor Atsushi Iwama, Lead Scientist, IMSUT
Focus on changes in aged HSC in the bone marrow niche
The research group investigated whether the rejuvenation of aged HSCs in the environment of a young bone marrow niche would be rejuvenated.
Tens of thousands of old hematopoietic stem / stem cells collected from 20-month-old mice were transplanted into 8-week-old young mice without prior treatment, such as radiation. After two months of follow-up, they collected bone marrow cells and performed flow cytometric analysis.
The research team also transplanted HSCs of 10-week-old young mice for comparison. In addition, embedded aged HSCs were fractionated and RNA sequence analysis and DNA methylation analysis were performed.
They found that implanted aged HSCs were less capable of producing hematopoietic cells than younger HSCs. They also showed that the differentiation of older HSCs into multipotent progenitor cells was persistently disrupted even in the young bone marrow niche, and that the direction of differentiation was biased. It has been found that the transfer of older HSCs into the niche of young bone marrow does not improve their stem cell function.
A more detailed analysis can reveal the mechanisms that irreversibly affect the aging function of HSC
HSC-targeted aging studies were actively conducted in mice using a bone marrow transfer model. However, the effect of aging on HSC remains to be elucidated.
Professor Iwama states: “This study has a significant impact because it has clarified the impact of aging on HSC. Our results are expected to contribute to further elucidating the mechanism of HSC aging and understanding the pathogenic mechanism of blood associated with age-related disease.”
Institute of Medical Sciences, University of Tokyo
Kuribayashi, W., and others. (2020) Limited rejuvenation of aged hematopoietic stem cells in a niche of young bone marrow. Journal of Experimental Medicine. doi.org/10.1084/jem.20192283.